Abstract
Uricase from Candida utilis, an enzyme containing essential thiol, was examined for its sensitivity to myeloperoxidase (MPO), an oxidant present in neutrophils. Upon exposure to a system composed of MPO, hydrogen peroxide and bromide at moderately acidic pH, but not at neutral to alkaline pH, the uricase lost almost all of its enzyme activity. Thus the MPO-H2O2-bromide system significantly inactivated uricase only at moderately acidic pH. This inactivation by the MPO system was prevented by the presence of N-acetylmethionine, a thioether compound, or glutathione, a thiol compound analogous to amino acid, the remaining uricase activity being respectively 86.0±2.0 and 81.0±2.0% (mean±SEM, n=5). These findings suggest that the inactivation was due to oxidation and damage of thio-group present in the catalytic site of uricase by the MPO system. They also suggest that methionine and glutathione modulate the strength of an oxidative stress by this MPO system. Therefore, it appears that these compounds are clinically applicable as a therapeutic antioxidant in leukocytoses such as inflammatory diseases and granulocytic leukemia.
